Randomized Controlled Trial of Mycophenolate Mofetil in Children, Adolescents, and Adults With IgA Nephropathy

Background Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results. Study Design Double-blind placebo-controlled randomized controlled trial. Setting & Participants 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6 g/g (males) or ≥0.8 g/g (females); and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2 (≥40 mL/min/1.73 m2 if receiving angiotensin-converting enzyme inhibitor). Mean age, 32 ± 12 (SD) years; 62% men; and 73% white. Intervention Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR ≥ 0.6 g/g (males) and ≥0.8 g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36 mg/kg/d) in addition to lisinopril/losartan plus Omacor. Outcomes Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment. Measurements UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula. Results 44 patients completed 6 months of treatment with MMF (n = 22) or placebo (n = 22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR < 0.2 g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was −0.22 (95% CI, −0.75 to 0.31; P = 0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew. Limitations Low patient enrollment and short follow-up. Conclusions MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor. Previous randomized controlled trials evaluating the efficacy of mycophenolate mofetil (MMF) in patients with immunoglobulin A nephropathy (IgAN) have produced varying results. Double-blind placebo-controlled randomized controlled trial. 52 children, adolescents, and adults with biopsy-proven IgAN in 30 centers in the United States and Canada. Entry criteria: age older than 7 to younger than 70 years; urine protein-creatinine ratio (UPCR), ≥0.6 g/g (males) or ≥0.8 g/g (females); and estimated glomerular filtration rate ≥ 50 mL/min/1.73 m2 (≥40 mL/min/1.73 m2 if receiving angiotensin-converting enzyme inhibitor). Mean age, 32 ± 12 (SD) years; 62% men; and 73% white. Lisinopril (or losartan) plus a highly purified omega-3 fatty acid (Omacor [Pronova Biocare]) was given to 94 patients for 3 months; 52 of the patients with persistent UPCR ≥ 0.6 g/g (males) and ≥0.8 g/g (females) were randomly assigned to MMF or placebo (target dose, 25-36 mg/kg/d) in addition to lisinopril/losartan plus Omacor. Change in UPCR after 6 and 12 months treatment with MMF/placebo and 12 months after the end of treatment. UPCR measured on 24-hour urine samples. Glomerular filtration rate estimated with the Schwartz (age < 18 years) or Cockcroft-Gault (age ≥ 18 years) formula. 44 patients completed 6 months of treatment with MMF (n = 22) or placebo (n = 22). The trial was terminated early at the recommendation of the Data Monitoring Committee because of the lack of benefit. No patient achieved a complete remission (UPCR < 0.2 g/g). Mean UPCRs at randomization and after 6 months were 1.45 (95% CI, 1.16-1.75) and 1.40 (95% CI, 1.09-1.70) for MMF and 1.41 (95% CI, 1.17-1.65) and 1.58 (95% CI, 1.13-2.04) for placebo, respectively. The mean difference in UPCR change between these groups (MMF minus placebo) was −0.22 (95% CI, −0.75 to 0.31; P = 0.4). Adverse events were rare apart from nausea (MMF, 8.7%; placebo, 3.7%); one of these MMF patients withdrew. Low patient enrollment and short follow-up. MMF did not reduce proteinuria significantly in patients with IgAN who had persistent proteinuria after lisinopril/losartan plus Omacor.